Ninety five percent of colorectal cancer develops by a well understood series of genetic mutations over a 10-15 year time frame beginning as a tissue growth, commonly termed a polyp. Approximately one third to one half of adults will develop one or more polyps over their lifetime, approximately ten percent of which will progress to colon cancer. Therefore the overwhelming majority of colorectal cancers can be avoided by identification and removal of polyps at an early stage before malignant conversion. Endoscopy is the predominant means by which the US population is screened for benign and pre- malignant colonic polyps. While colonoscopy can detect up to 95% of cancerous lesions, polyps are missed approximately 25% of the time utilizing current standard and enhanced techniques. Our preliminary studies have established a quantitatively measurable difference in tissue oxygenation between pre-malignant polyps and normal colonic tissue. The proposed research further develops a system to exploit this physiologic contrast with an ultimate goal of reducing colon cancer through improved detection of polyps during screening colonoscopy while maintaining clinical efficiency. There is currently no clinically practical method of quantitativel assessing tissue oxygenation during colonoscopy or method of using such information to improve neoplastic polyp detection. The proposed system utilizes an imaging bundle that extends through the working channel of a traditional colonoscope to detect and quantitatively measure oxygen differences that exist in polyps when compared to normal colonic tissue. The system will highlight suspicious lesions on traditional scope video images using graphic overlay. If a suspicious lesion is identified the system will allow for exchange of the imaging bundle for another instrument, while retaining / tracking the lesion highlighted on the video monitor. The research effort commences with the development of an ideal testbed system to overcome limitations experienced during feasibility studies. The testbed will be utilized to study and optimize sensing technique and determine critical design inputs using both bench top and in-vivo testing in a proven rodent model of genetically induced colonic neoplasms. The results will feed forward into development of a commercial candidate meeting established design requirements while maintaining commercial viability. The commercial candidate will be validated in a gene-mapped porcine model of colon cancer, and evaluated against other relevant colonoscopy technologies and pathological truth to test the hypothesis that mapping tissue oxygenation, during video colonoscopy, can more readily detect neoplastic / pre-neoplastic lesions. The system developed and data obtained in this effort will form the basis to apply for investigational device exemption to conduct first-in-man trials.